Scavenger Receptor Class B Type I Protein as an Independent Predictor of High-Density Lipoprotein Cholesterol Levels in Subjects with Hyperalphalipoproteinemia
Open Access
- 1 April 2009
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 94 (4), 1451-1457
- https://doi.org/10.1210/jc.2008-1223
Abstract
Context: In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol (HDL-C) levels. Objective: Our objective was to determine the relationship between SR-BI protein and HDL-C levels in humans. Design: This was a prospective study of adults with hyperalphalipoproteinemia. Fasting blood was obtained for lipid and lipoprotein measurement, genomic DNA, and monocyte-derived macrophages. SR-BI protein levels were measured by Western blots, and SR-BI activity was measured by cholesteryl ester (CE) uptake of each donor’s radiolabeled HDL with their monocyte-derived macrophages, or by degradation and specific cell association of dual-labeled HDL in vitro. Setting: The study was performed in a tertiary university teaching hospital. Results: The mean age was 57.2 ± 10.9 yr (n = 65). SR-BI protein levels were inversely associated with HDL-C levels (P < 0.002), HDL particle size (P < 0.05), and positively associated with CE uptake (P < 0.004); there was no association with plasma apolipoprotein levels. SR-BI protein levels (P = 0.01) were independent predictors of HDL-C levels. Subjects who were carriers of the A allele for the rs4238001 (glycine to serine at position 2) polymorphism [single nucleotide polymorphism (SNP)] had lower SR-BI protein levels (P = 0.01), whereas carriers of the C allele for the rs2278986 SNP also had lower SR-BI protein levels (P = 0.02). Body mass index (P = 0.05), rs4238001 (P = 0.01), and rs2278986 (P = 0.01) SNPs were independent predictors of SR-BI protein levels. In vitro studies of murine macrophages stably expressing the glycine to serine at position 2 SNP showed less degradation (P < 0.0004) and specific cell association (P < 0.0004) of [125I, 3H]-CE-labeled HDL. Conclusions: SR-BI protein has an independent effect on HDL-C levels in women with hyperalphalipoproteinemia. Two SNPs were significantly associated with lower SR-BI protein levels.Keywords
This publication has 35 references indexed in Scilit:
- Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivoJCI Insight, 2007
- Variants in Scavenger Receptor Class B Type I Gene Are Associated with HDL Cholesterol Levels in Younger WomenHuman Heredity, 2007
- Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo StudyAtherosclerosis, 2005
- Association Between a Novel 11–Base Pair Deletion Mutation in the Promoter Region of the Scavenger Receptor Class B Type I Gene and Plasma HDL Cholesterol Levels in Taiwanese ChineseArteriosclerosis, Thrombosis, and Vascular Biology, 2003
- Leptin Induces the Hepatic High Density Lipoprotein Receptor Scavenger Receptor B Type I (SR-BI) but Not Cholesterol 7α-Hydroxylase (Cyp7a1) in Leptin-deficient (ob/ob) MicePublished by Elsevier BV ,2003
- Association of genetic variants in the HDL receptor, SR-B1, with abnormal lipids in women with coronary artery diseaseJournal of Medical Genetics, 2003
- Dietary myristic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamsterBritish Journal of Nutrition, 2002
- Increasing amounts of dietary myristic acid modify the plasma cholesterol level and hepatic mass of Scavenger receptor BI without affecting bile acid biosynthesis in hamstersReproduction Nutrition Development, 2002
- Epidemiological aspects of high density lipoprotein cholesterolAtherosclerosis, 1998
- High-Density Lipoprotein — The Clinical Implications of Recent StudiesNew England Journal of Medicine, 1989